Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.
A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.
Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through different protein interactions. The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors.
Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behavior. It entails research of mechanisms of neuropathology, pharmacodynamics, psychiatric illness, and states of consciousness. These studies are instigated at the detailed level involving neurotransmission/receptor activity, bio-chemical processes, and neural circuitry. Neuropsychopharmacology supersedes psychopharmacology in the areas of "how" and "why", and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments. Developments in neuropsychopharmacology may directly impact the studies of anxiety disorders, affective disorders, psychotic disorders, degenerative disorders, eating behavior, and sleep behavior.
Cocaine- and amphetamine-regulated transcript, also known as CART, is a neuropeptide protein that in humans is encoded by the CARTPT gene. CART appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant.
Troparil is a stimulant drug used in scientific research. Troparil is a phenyltropane-based dopamine reuptake inhibitor (DRI) that is derived from methylecgonidine. Troparil is a few times more potent than cocaine as a dopamine reuptake inhibitor, but is less potent as a serotonin reuptake inhibitor, and has a duration spanning a few times longer, since the phenyl ring is directly connected to the tropane ring through a non-hydrolyzable carbon-carbon bond. The lack of an ester linkage removes the local anesthetic action from the drug, so troparil is a pure stimulant. This change in activity also makes troparil slightly less cardiotoxic than cocaine. The most commonly used form of troparil is the tartrate salt, but the hydrochloride and naphthalenedisulfonate salts are also available, as well as the free base.
(–)-2β-Carboisopropoxy-3β-(4-iodophenyl)tropane is a stimulant drug used in scientific research, which was developed in the early 1990s. RTI-121 is a phenyltropane based, highly selective dopamine reuptake inhibitor and is derived from methylecgonidine. RTI-121 is a potent and long-lasting stimulant, producing stimulant effects for more than 10 hours after a single dose in mice which would limit its potential uses in humans, as it might have significant abuse potential if used outside a medical setting. However RTI-121 occupies the dopamine transporter more slowly than cocaine, and so might have lower abuse potential than cocaine itself.
Psychological dependence is a cognitive disorder that involves emotional–motivational withdrawal symptoms—e.g. anxiety and anhedonia—upon cessation of prolonged drug abuse or certain repetitive behaviors. It develops through frequent exposure to a psychoactive substance or behavior, though behavioral dependence is less talked about. The specific mechanism involves a neuronal counter-adaptation, which could be mediated through changes in neurotransmitter activity or altered receptor expression. Environmental enrichment and physical activity can attenuate withdrawal symptoms.
LR-5182 is a stimulant drug which acts as a norepinephrine–dopamine reuptake inhibitor, structurally related to the better known drug fencamfamine. It was developed by the pharmaceutical company Eli Lilly in the 1970s, and researched for potential use as an antidepressant, although never marketed. LR-5182 has two stereoisomers, both of which are active, although one isomer blocks reuptake of only dopamine and noradrenaline, while the other blocks reuptake of serotonin as well.
RTI(-4229)-150, is a phenyltropane derivative which acts as a potent dopamine reuptake inhibitor and stimulant drug. It is around 5x more potent than cocaine, but is more selective for the dopamine transporter relative to the other monoamine transporters. RTI-150 has a fast onset of effects and short duration of action, and its abuse potential in animal studies is similar to that of cocaine itself; its main application in scientific research has been in studies investigating the influence of pharmacokinetics on the abuse potential of stimulant drugs, with the rapid entry of RTI-150 into the brain thought to be a key factor in producing its high propensity for development of dependence in animals. RTI-150 is not explicitly illegal anywhere in the world, but its similar structure and pharmacological activity to cocaine makes it possible that it would be considered a controlled substance analogue in countries such as the US, Canada, Australia and New Zealand which have controlled substance analogue legislation.
RTI-126 is a phenyltropane derivative which acts as a potent monoamine reuptake inhibitor and stimulant drug, and has been sold as a designer drug. It is around 5 times more potent than cocaine at inhibiting monoamine reuptake in vitro, but is relatively unselective. It binds to all three monoamine transporters, although still with some selectivity for the dopamine transporter. RTI-126 has a fast onset of effects and short duration of action, and its pharmacological profile in animals is among the closest to cocaine itself out of all the drugs in the RTI series. Its main application in scientific research has been in studies investigating the influence of pharmacokinetics on the abuse potential of stimulant drugs, with its rapid entry into the brain thought to be a key factor in producing its high propensity for development of dependence in animals.
RTI(-4229)-336, is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine transporter with around 20x the affinity of cocaine, however it produces relatively mild stimulant effects, with a slow onset and long duration of action. These characteristics make it a potential candidate for treatment of cocaine addiction, as a possible substitute drug analogous to how methadone is used for treating heroin abuse. RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, and significantly reduces rates of cocaine use, especially when combined with SSRIs, and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
(–)-2β-Carbomethoxy-3β-(4-bromophenyl)tropane is a semi-synthetic alkaloid in the phenyltropane group of psychostimulant compounds. First publicized in the 1990s, it has not been used enough to have gained a fully established profile. RTI-51 can be expected to have properties lying somewhere in between RTI-31 and RTI-55. It has a ratio of monoamine reuptake inhibition of dopamine > serotonin > norepinephrine which is an unusual balance of effects not produced by other commonly used compounds. It has been used in its 76Br radiolabelled form to map the distribution of dopamine transporters in the brain.
Yasmin Hurd is the Ward-Coleman Chair of Translational Neuroscience and the Director of the Addiction Institute at Mount Sinai. Hurd holds appointments as faculty of Neuroscience, Psychiatry, Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai in New York City and is globally recognized for her translational research on the underlying neurobiology of substance use disorders and comorbid psychiatric disorders. Hurd's research on the transgenerational effects of early cannabis exposure on the developing brain and behavior and on the therapeutic properties of cannabidiol has garnered substantial media attention. In 2017, Dr. Hurd was elected to the National Academy of Medicine and, in 2022, Dr. Hurd was elected to the National Academy of Sciences (NAS).
Nancy Rutledge Zahniser was an American pharmacologist, best known for her work involving the mechanism of dopaminergic pathways and chemical modifications of them. Although born in Ann Arbor, Michigan, Zahniser grew up in Chillicothe, Ohio and subsequently enrolled at the College of Wooster, where she obtained a degree in chemistry. After completing her degree, Zahniser spent some time in India where she met her first husband Mark Zahniser; she later returned to the United States to attend the University of Pittsburgh School of Pharmacy, where she earned her PhD in pharmacology in 1977. Zahniser went on to complete her post-doctoral training at the University of Colorado Health Sciences Center's Department of Pharmacology and then became a part of the faculty there. In 2007, she became associate dean for research education. She played a role in advancing the careers of many post-doctoral students in her lab. In addition to her work as a professor, Zahniser was also a member of several boards, committees, review panels, and professional societies related to pharmacology, neuroscience, and addiction. She led several national research meetings from 1995-2002.
James David Jentsch is an American neuroscientist. He is the Empire Innovation Professor of Psychology at Binghamton University. His research considers the neurobiological origins of psychoses and addiction. Jentsch was awarded the 2011 AAAS Award for Scientific Freedom and Responsibility.
Bita Moghaddam is an Iranian-American neuroscientist and author. She is currently the Ruth Matarazzo Professor of Behavioral Neuroscience at Oregon Health & Science University. Moghaddam investigates the neuronal processes underlying emotion and cognition as a first step to designing strategies to treat and prevent brain illnesses.
Marina Elizabeth Wolf is an American neuroscientist and Professor of Behavioral Neuroscience at Oregon Health & Science University. Previously she served as Professor and Chair of the Department of Neuroscience in the Chicago Medical School at Rosalind Franklin University of Medicine and Science. She has been a pioneer in studying the role of neuronal plasticity in drug addiction. Her laboratory is particularly interested in understanding why individuals recovering from substance use disorder remain vulnerable to drug craving and relapse even after long periods of abstinence.
Eva King Killam was a research pharmacologist who studied the activity of drugs on the brain and behavior, developing animal models for epilepsy and opiate dependence.
Terry Earl Robinson is a biopsychologist and neuroscientist, and the Elliot S. Valenstein Distinguished University Professor of Psychology & Neuroscience at The University of Michigan.
